Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

Abstract

In its rare occurrence, Langerhans cell histiocytosis (LCH) is a dangerous but intriguing deviation of mononuclear phagocytes, especially dendritic cells (DCs). Clinically, the disease ranges from self-resolving or well manageable to severe and even fatal. LCH lesions in skin, bone, and other sites contain high numbers of cells with phenotypic features resembling LCs admixed with macrophages, T cells, eosinophils, and multinucleated giant cells. Here we review current progress in the LCH field based on two central questions: (i) are LCH cells intrinsically aberrant, and (ii) how does the lesion drive pathogenesis? We argue that LCH cells may originate from different sources, including epidermal LCs, tissue Langerin(+) DCs, or mononuclear phagocyte precursors. Current and prospective in vitro and in vivo models are discussed. Finally, we discuss recent insights into plasticity of T-helper cell subsets in light of the lesion microenvironment. LCH continues to provide urgent clinical questions thereby inspiring innovative DC lineage research.

Langerhans cell histiocytosis shows distinct cytoplasmic expression of major histocompatibility class II antigens

“…Our observation of the absence of MHCII cell surface expression in LCH is consistent with previously published evidence of LCH cell immaturity (17;18). Other studies have described high intracellular MHCII labeling in normal (benign) resident LCs with MHCII predominantly localized in the lysosome-like MIIC compartment, and in lower amounts on the membranes of the RER.…”

Resorption of PDLLA Plates as a Nidus for Recurrent Langerhans Cell Histiocytosis

“…The lesions typically occur in one or more organ systems, most typically bone [2,6,16,17] and skin (dermis), as well as viscera, e.g. lung and liver [18,19]. In single system disease, the course is generally benign, responding to local therapy; with the involvement of multiple organ systems, the disease can be aggressive and fatal despite multimodal therapy [5,19,20,21,22].…”

“…Normally, Langerhans cells originate in the bone marrow. However, these cells may then migrate to lesions due to cytokine release, or may develop and proliferate within the lesions [18]. LCH can behave as a neoplasm, with aggressive spread in the setting of mutations of tumor suppressor genes, familial clustering and growing in clonal populations [18,23].…”

“…However, these cells may then migrate to lesions due to cytokine release, or may develop and proliferate within the lesions [18]. LCH can behave as a neoplasm, with aggressive spread in the setting of mutations of tumor suppressor genes, familial clustering and growing in clonal populations [18,23]. After resection of visceral LCH, recurrence in the transplanted organs has been reported, which is particularly notable considering the strong immunosuppression required for lung and liver transplants [24,25].…”

Review of Rosai-Dorfman Disease: New Insights into the Pathogenesis of This Rare Disorder

“…It has been generally known that HIV infection, autoimmune hemolytic anemia, IgG4-related disease, and autoimmune disease are closely linked to immunologic derangements. Recent studies have also demonstrated that both lymphoma and LCH have to do with the specific immune response [59,60,61]. The transcription factor T-bet could regulate the maintenance of immune homeostasis [62].…”